Infections in the golden hamster with Leishmania donovani are being used as models for the study of immunity to visceral leishmaniasis. Since the hamster is one of the few hosts in which parasites will visceralize to the liver and spleen from a cutaneous site of inoculation, it will be utilized to study the effect of Leishmania strain virulence on the ability to produce patent visceral infection. Attempts will be made to determine the relative importance of initial dermal infections in the development of immunity against kala-azar and whether the time of visceralization from a cutaneous site has any effect on the development of an acquired immune response. Subcutaneous infections will be used to stimulate immunity and will be followed at various intervals by an intracardial injection with low numbers of parasites to mimic the process of visceralization from cutaneous site. These animals will then be challenged with larger numbers of organisms to assess their state of acquired resistance. Efforts will also be made to determine if the immune reactions in the hamster affect parasite reproduction or if resistance is associated with an increased capacity by the hamster to kill the parasite. These studies will involve the fate of radiolabelled parasites in vivo as well as their fate within in vitro macrophage cultures. Finally, the ability of parasite products to induce blastogenesis of host lymphoid cells will be investigated in order to determine if the hypergammaglobulinemia seen in infected hamsters is associated with possible parasite mitogenic effects on these cells.